Linked Life Data

20158191

Source:http://linkedlifedata.com/resource/pubmed/id/20158191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-3-4
pubmed:abstractText
GPVI is a key receptor for collagen-induced platelet activation. Loss or inhibition of GPVI causes only mildly prolonged bleeding times but prevents arterial thrombus formation in animal models. Therefore, GPVI is considered to be a potent target molecule for therapy of thrombotic diseases. Recently, it was reported that the AT(1)-receptor antagonist losartan (DuP-753) and EXP3179 inhibit platelet adhesion and aggregation via GPVI. However, it is still not clear how losartan is associated with inhibition of binding between GPVI and collagen at the molecular level. Here, we show by NMR that losartan directly interacts with the hydrophobic region consisting of strands C' and E in the N-terminal Ig-like domain of GPVI. A reliable GPVI-losartan complex model is presented by using a combination of NMR data and in silico tools. These data indicated that the phenyl group with the tetrazole ring in losartan plays a crucial role in the interaction with GPVI.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-4804
pubmed:author
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2087-93
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Structural basis for platelet antiaggregation by angiotensin II type 1 receptor antagonist losartan (DuP-753) via glycoprotein VI.
pubmed:affiliation
Japan Biological Informatics Consortium (JBIC), Aomi 2-41-6, Tokyo 135-0064, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't